Cancer remains one of the most important unmet medical challenges to mankind. A number of options for treating tumors are available, including surgery, radiation, chemotherapy, or any combination of these approaches. Among these, chemotherapy is widely used for all types of cancers, in particular for those inoperable or with metastatic characteristics. Despite a variety of chemotherapeutic compounds being used in clinics, chemotherapy is generally not curative, but only delays disease progression. Commonly, tumors and their metastasis become refractory to chemotherapy, as the tumor cells develop the ability of multidrug resistance. In some cases, the tumors are inherently resistant to some classes of chemotherapeutic agents. In other cases, the acquired resistance against chemotherapeutic agents is developed during the chemotherapeutic intervention. Thus, there remain significant limitations to the efficacy of available chemotherapeutic compounds in treating different classes of tumors. Furthermore, many cytotoxic and cytostatic agents used for chemotherapeutic treatment of tumors have severe side effects, resulting in termination of the chemotherapy in some patients. Thus, there remains a need for new chemotherapeutic agents.
Dibenzyl trisulfide (DBTS) is a biologically active polysulfide secondary metabolite that was isolated from the sub-tropical shrub, Petiveria alliacea L. (Phytolaccaceae). It has been reported that DBTS has immunomodulatory activities (“Immunomodulatory activities of Petiveria alliacea.”, by Williams, L. A. D., Gardner, T. L., Fletcher, C. K., Naravane, A., Gibbs, N. and Fleischhacker, R. Phytother. Res., 1997, 11, 251-253; “A sulfonic anhydride derivative from dibenzyl trisulphide with agro-chemical activities”, by Williams, L. A. D., Vasquez, E., Klaiber, I., Kraus, W. and Rosner, H. Chemosphere, 2003, 51, 701-706). In investigating the cellular and molecular mechanisms of DBTS for its immunomodulatory activity, Rosner and co-workers reported that DBTS preferentially binds to an aromatic region of bovine serum albumin and attenuates the dephosphorylation of tyrosyl residues of MAP kinase (erk1/erk2) in SH-SY5Y neuroblastoma cells (in “Disassembly of microtubules and inhibition of neurite outgrowth, neuroblastoma cell proliferation, and MAP kinase tyrosine dephosphorylation by dibenzyl trisulphide”, by Rosner, H., Williams, L. A. D., Jung, A. and Kraus, W. Biochim. Biophy. Acta, 2001, 1540, 166-177). In addition, they reported that DBTS causes a reversible disassembly of microtubules and did not affect actin dynamics in SH-SY5Y neuroblastoma cells and in Wistar 38 human lung fibroblasts. Furthermore, they reported that DBTS also inhibits neuroblastoma cell proliferation and neurite outgrowth from spinal cord explants.
In a different study, Mata-Greenwood and co-workers tested the antiproliferative and differentiating activity of a large set of extracts derived from various plants (“Discovery of novel inducers of cellular differentiation using HL-60 promyeolocytic cells”, by Mata-Greenwood, E., Ito A., Westernburg, H., Cui, B., Mehta, R. G., Kinghorn, A. D. and Pezzuto, J. M. Anticancer Res. 2001, 21, 1763-1770). They reported that the lipophilic extract of the roots of Petiveria alliacea L., and the active fraction from the lipophilic extract showed antiproliferative and differentiating activity in HL-60 promyelocytic cells. From the active fraction of the lipophilic extract, they isolated two active organosulfur compounds, i.e., 2-[(phenylmethyl)dithio]ethanol and dibenzyl trisulfide. They reported that these two organosulfur compounds induced monocyte-like differentiation and strong cytotoxicity. Furthermore, they reported that none of these two isolates demonstrated antiproliferative activity in HL-60 cells.